In Situ Detection of Nucleic Acids in Extracellular Vesicles via Membrane Fusion.

Extracellular vesicles (EVs) carry diverse biomolecules (e.g., nucleic acids, proteins) for intercellular communication, which can serve as important markers for diseases. Analyzing nucleic acids sourced from EVs enables non-invasive disease diagnosis and prognosis evaluation. Membrane fusion, a fundamental cellular process merging two lipid membranes, facilitates cell communication and cargo transport. Drawing inspiration from this natural phenomenon, recent years have witnessed the emergence of membrane fusion-based strategies for the detection of nucleic acids within EVs. These strategies entail the encapsulation of detection probes within either artificial or natural vesicles, which subsequently undergo membrane fusion with EVs. This innovative approach enables the in situ detection of nucleic acids within EVs while maintaining the structural integrity of EVs, thus preventing nucleic acid degradation and minimizing interference from free nucleic acids. This review categorizes approaches into universal and target membrane fusion approaches, and discusses the challenges and future prospects associated with EV nucleic acids detection using membrane fusion.